PUBLICATION

A zebrafish model of infection-associated acute kidney injury

Authors
Wen, X., Cui, L., Morrisroe, S., Maberry, D., Emlet, D.R., Watkins, S.C., Hukriede, N.A., Kellum, J.A.
ID
ZDB-PUB-180315-5
Date
2018
Source
American journal of physiology. Renal physiology   315(2): F291-F299 (Journal)
Registered Authors
Hukriede, Neil
Keywords
acute kidney injury, innate immunity, sepsis, zebrafish larvae
MeSH Terms
  • Acute Kidney Injury/immunology
  • Acute Kidney Injury/metabolism
  • Acute Kidney Injury/microbiology*
  • Acute Kidney Injury/pathology
  • Animals
  • Animals, Genetically Modified
  • Disease Models, Animal
  • Edwardsiella tarda/immunology
  • Edwardsiella tarda/pathogenicity*
  • Enterobacteriaceae Infections/immunology
  • Enterobacteriaceae Infections/microbiology*
  • Gene Expression Regulation
  • Host-Pathogen Interactions
  • Immunity, Innate
  • Larva
  • Nephrons/immunology
  • Nephrons/metabolism
  • Nephrons/microbiology*
  • Nephrons/pathology
  • Sepsis/immunology
  • Sepsis/metabolism
  • Sepsis/microbiology*
  • Sepsis/pathology
  • Signal Transduction
  • Zebrafish*/embryology
  • Zebrafish*/genetics
  • Zebrafish*/metabolism
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed
29537312 Full text @ Am. J. Physiol. Renal Physiol.
Abstract
Sepsis-associated acute kidney injury (S-AKI) independently predicts mortality among critically ill patients. The role of innate immunity in this process is unclear, and there is an unmet need for S-AKI models to delineate the pathophysiological response. Mammals and zebrafish (Danio rerio) share a conserved nephron structure and homologous innate immune systems, making the latter suitable for sepsis-associated AKI research. We introduced Edwardsiella tarda (E.tarda) to the zebrafish. Systemic E. tarda bacteremia resulted in sustained bacterial infection and dose-dependent mortality. A systemic immune reaction was characterized by increased mRNA expressions of il-1β, tnfα, tgfβ1a, and cxcl8-l1 (P<0.0001, P<0.001, P<0.001, and P<0.01, respectively). Increase of host stress responsive gene ccnd1 and tp53 were observed at 24h post-injection (P<0.0001 and P<0.05, respectively). Moderate E.tarda infection induced zebrafish mortality of over 50% in larvae and 20% in adult, accompanied by pericardial edema in larvae and renal dysfunction in both larvae and adult zebrafish. Expression AKI injury marker IGFBP-7, TIMP-2, and KIM-1 were found significantly increased in the septic animals at transcription level (P<0.01, P<0.05, and P<0.05) and nephric tubule expressions compared to non-infected animals. Pathway analysis suggested IGFBP-7 and TIMP-2 antagonize KIM-1 on cell migration and phagocyte movement; IGFBP-7 and KIM-1 inhibit cell differentiation after injury. In conclusion, we established a zebrafish model of S-AKI induced by E.tarda injection, with both larvae and adult zebrafish showed nephron injury in the setting of infection.
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